NF1

NF1 is the most common of the rare genetic conditions which come under the umbrella of neurofibromatosis. NF1 affects up to 1 in 2,500 people. Features and symptoms usually appear in the first few years of life.

NF1 is usually easily diagnosed by clinical examination and taking down a family history of medical concerns and skin issues. NF1 is an extremely variable condition. Some people have it so mildly they do not know they have it, and others can require minor medical intervention or have life-threatening complications. This is true even within a family who has multiple members affected by the condition. There is currently no way of knowing or predicting the severity of a person’s symptoms or which symptoms and features they will have.

CAFÉ AU LAIT SPOTS: The most common feature of NF1 is the café au lait spots or patches, which appear at birth or within the first couple of years of life. These are brown coloured ‘birthmarks”, which are flat and cause no symptoms or concerns. They are just an indicator of the condition. Diagnosis requires 6 or more of these café au lait patches, and they must be larger than 0.5 cm in diameter in children or 1.5 cm in adults.

NEUROFIBROMAS: the hallmark of NF1 neurofibromas do not usually appear until later. They are small, pea shaped, rubbery feeling benign lumps (tumours) which develop on or just under the skin. They may also develop deeper within the body. While a few children will have neurofibromas from a young age most people affected often begin to notice neurofibromas from around the time of puberty onwards. The number may increase with age, and women affected have indicated that the number and size of these tumours can increase during pregnancy. Some people will have only a couple of neurofibromas, while others can have them all over their body. The general population do get neurofibromas, but usually only a single case, so the presence of multiple (2 or more) neurofibromas can lead to diagnosis of NF1 in conjunction with at least one other feature of the condition. These tumours never become cancerous.

LISCH NODULES: Lisch nodules are small tumours which develop on the iris. They do not cause symptoms, and are a clinical indicator for NF1. They usually develop before the age of 10, and nearly all people affected by NF1 will have them by the age of 20. Lisch nodules can often be seen without aids, but sometimes an examination using a slit lamp may be required to distinguish them from other normal parts of the iris.

FRECKLING: Another common feature of NF1, is freckling in strange places like under the arms and in the groin area. Again, there are no symptoms arising from this feature, but freckling is an indicator for the condition.

Aside from these common features of NF1 there are also features which can be symptomatic, and do from time to time require medical intervention. These include, plexiform neurofibromas, optic pathway gliomas, skeletal abnormalities, learning disabilities and epilepsy.

It is, however, important to remember that most people with NF1 remain well and lead normal lives.

PLEXIFORM NEUROFIBROMAS: Benign tumours that develop on peripheral nerves, and tend to grow over large areas involving a whole section of a nerve including its branches. They often appear as a lumpy mass under the skin. They can occur anywhere in the body, including deep within the body. The skin that overlies them can often be thickened, pigmented or hairy. This specific type of neurofibroma often develops much earlier than the skin (dermal) neurofibromas described above, and develop in approximately 30 - 50% of those diagnosed with NF1. These plexiform neurofibromas need to be monitored as they can become malignant. Malignancy is most common during a person’s 20s and 30s. See more about this below.

OPTIC PATHWAY GLIOMA (OPG): This is a swelling (tumour) of the nerve which controls vision. In over half of the 15 – 20% of children who have NF1 with these tumours do not ever have any symptoms, without careful monitoring by an ophthalmologist (eye doctor) they can go on to cause problems with eyesight. The presence of an OPG can sometimes confirm the diagnosis of NF1. Guidelines recommend a yearly eye exam by an ophthalmologist until at least age 8 with less frequent monitoring after that point as this is when the chance of developing a symptomatic OPG eases off.

SKELETAL ABNORMALITIES: There are two types of very rare skeletal abnormalities that children with NF1 can have. They generally are present at birth or soon after. The long bones in the arms and legs sometimes do not develop properly, and can appear more curved than is normal, which may not require treatment. Pseudoarthrosis, or the formation of a false joint caused by fracture, is the extreme and sometimes occurs in the long bones e.g. tibia and radius, due to the way in which the bones develop. Sphenoid wing dysplasia relates to the abnormal development of bones in the eye socket. These complications will require supervision and possibly treatment from an orthopaedic surgeon (bone doctor).

LEARNING DISABILITIES: Approximately half of all children given a diagnosis of NF1 will have some sort of learning or attention difficulties. Despite this large percentage it is rare for children with NF1 to have a diagnosis of intellectual disability. Children with NF1 can struggle with speech and language, concentration, perception of space, following instructions and co-ordination. Their behavior can be erratic, impulsive and inconsistent. They may not understand social cues or reasoning behind appropriate behaviours. These learning problems are not unique to NF1 and are dealt with in the same way as other children without NF1.

EPILEPSY: 3-7% of children with a diagnosis of NF1 also have epilepsy according to research. The epileptic seizures suffered by those with NF1 are the same as those suffered by anyone with epilepsy/seizures in the general population and therefore are treated in the same way.

Information about the diagnostic criteria for NF1 can be found on our Diagnosis page.

These cancers can also form spontaneously, and so everyone with NF1 needs to watch for:

Rapidly growing lumps under the skin

New and painful lumps under the skin

Unexplainable and persistent pain.

In both cases, where a plexiform is present and when a lump grows spontaneously and any of the above changes occur it is very important to see your doctor

OTHER TUMOURS/CANCERS: People with NF1 have a 1 in 10 chance (10%) of developing an NF1 related cancer across their lifetime. Adults with NF1 are known to have a slightly increased risk for developing glomus tumours, brain tumours, breast cancer, gastrointestinal stromal tumours (GIST), pheochromocytoma (rare, benign tumour of the adrenal glands) compared to the general population. Children also have an increased risk of a rare form of leukaemia and a tumour that grows near the bladder (rhabdomyosarcoma).

HIGH BLOOD PRESSURE: Guidelines indicate it is very important for anyone with NF1 to have their blood pressure monitored on a yearly basis. While people with NF1 are just as likely as someone not affected by NF1 to have high blood pressure for unknown reasons, there are two rare conditions affecting people with NF1 that makes monitoring of blood pressure especially important. As noted above, pheochromocytoma, a tumour that grows on the adrenal glands above the kidneys, if present causes an increase in blood pressure. Similarly, a narrowing in the arteries that lead to the kidneys (renal artery stenosis) results in increased blood pressure.

The above is not a definitive list of associated features and complications, but rather an outline of the more common ones associated with NF1. More detail can be found by visiting Factsheets.

In Australia, most medical professionals will only conduct scans (e.g. MRI) in NF1 when symptoms indicate there may be something to investigate. Each clinic and doctor will have a slightly different stance on this.

The condition is caused by a change in the spelling of a gene on chromosome 17. NF1 is a different condition to NF2, so if you have NF1 you will not develop NF2. This is because NF1 and NF2 are caused by different changes in spelling of two different genes. The conditions are similar in that they can both be either inherited from a parent or start with no previous family history. Each time a person with NF1 has a child, that child has a 1 in 2 (or 50%) chance of inheriting the condition. See Genetics for more information.

Mosaic or segmental NF1 is sometimes diagnosed in people with features of NF1 which only appear on one part of their body. This diagnosis is much less common than “generalised” NF1.